Epstein-Barr virus (EBV) is a lymphotropic gamma-herpesvirus that infects mostly B cells and is responsible for inducing their uncontrolled cell proliferation and transformation (Kieff (1996) in Virology, Fields, Knipe, and Howley, eds. Lipincott-Raven Publishers, New York, p. 2343). Under normal circumstances and in healthy individuals, EBV infections are not life threatening and generally are controlled by the immune system through the action of antigen-specific T-lymphocytes (Rickinson and Moss (1997) Annu. Rev. Immunol. 15:405). Both CD8+ cytotoxic T lymphocytes (CTL) and CD4+ helper T lymphocytes (HTL) can discriminate EBV-infected or EBV-transformed B cells and as a consequence, are able to inhibit their growth. EBV-specific T lymphocytes recognize antigen as molecular complexes formed by viral peptide epitopes with major histocompatibility complex (MHC) molecules, which are expressed on the surface of the infected/transformed B lymphocytes.
Although lifetime immunity to EBV apparently is achieved in normal individuals, the virus persists in a latent infection state (Nalesnik (1998) Springer Semin. Immunopathol. 20:325; Rowe (1999) Front. Biosci. 4:D346; and Babcock et al. (1998) Immunity 9:395), which effectively is controlled by EBV-specific T lymphocytes (Rickinson and Moss, supra). In immunosuppressed individuals such as transplant patients, however, primary EBV-infection usually results in post-transplant lymphoproliferative disorders (PTLD) that often progress into B-cell lymphomas (Hsieh et al. (1999) Transpl. Infect. Dis. 1:204; Hopwood and Crawford (2000) J. Clin. Pathol. 53:248; and Paya et al. (1999) Transplantation 68:1517). Current prophylactic and therapeutic approaches for PTLD and lymphomas are far from optimal.